Volume 4, Number 36;  October 5, 2005

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Patient: 44 year-old female with history of alcohol abuse, presenting with toothache. Routine laboratory testing revealed markedly elevated AST and ALT.

Session Handout:

Clinical Question: 

1) How is acetaminophen intoxication or poisoning managed?

Readings:

Link Directly to Fulltext Article at Publisher

<8>

Unique Identifier [PMID]: 15239079

Authors: Rumack BH.

Institution: University of Colorado School of Medicine, Greenwood Village, CO 80121, USA. barry@rumack.com

Title: Acetaminophen misconceptions.[see comment]. [Review] [55 refs]

Comments Comment in: Hepatology. 2004 Jul;40(1):23-6; PMID: 15239082, Comment in: Hepatology. 2004 Oct;40(4):1021-2; discussion 1022; PMID: 15382156

Source: Hepatology. 40(1):10-5, 2004 Jul.

Abstract: Examination of the pharmacokinetics of acetaminophen can decrease misconceptions involved in clinical evaluation. Enzyme patterns and acetaminophen levels must be related to time and known metabolic phenomena. A careful look at ethanol and nutrition, especially fasting demonstrates that therapeutic doses of acetaminophen do not place patients at a greater risk in either of these instances. An overdose of acetaminophen in a chronic alcohol abuser may result in more severe hepatotoxicity than in the nonalcoholic. CYP2E1 and glutathione must be evaluated simultaneously rather than in isolation. Glucuronidation capacity in humans is not a factor except in massively overdosed patients. [References: 55]

Publication Type: Journal Article. Review. Review, Tutorial.

 Link Directly to Fulltext Article at Science Direct

<16>

Unique Identifier [PMID]: 12706999

Authors: Dargan PI. Jones AL.

Institution: National Poisons Information Service, Guy's & St Thomas' NHS Trust, Avonley Road, London SE14 5ER, UK. paul.dargan@gstt.sthames.nhs.uk

Title: Management of paracetamol poisoning. [Review] [25 refs]

Source: Trends in Pharmacological Sciences. 24(4):154-7, 2003 Apr.

Abstract: Paracetamol is the most common substance involved in self-poisoning in the UK. The main advances made over the past five years in the management of early paracetamol poisoning, identification of risk factors for paracetamol poisoning, understanding of the mechanisms and management of late paracetamol poisoning and issues concerning the prevention of paracetamol poisoning are discussed. [References: 25]

Publication Type: Journal Article. Review. Review, Tutorial.

 Link Directly to Fulltext article in Ovid

<19>

Unique Identifier [PMID]: 12137690

Authors: Brok J. Buckley N. Gluud C.

Institution: Centre for Clinical Intervention Research, Copenhagen University Hospital, Department 71-02, H:S Rigshospitalet, Copenhagen O, Denmark, DK 2100. jesperb@mdb.ku.dk

Title: Interventions for paracetamol (acetaminophen) overdoses. [Review] [114 refs]

Source: Cochrane Database of Systematic Reviews. (3):CD003328, 2002.

Abstract: BACKGROUND: Self-poisoning with paracetamol (acetaminophen) is a common cause of hepatotoxicity in the Western World. Interventions for paracetamol poisoning encompass inhibition of absorption, removal from the vascular system, antidotes, and liver transplantation. OBJECTIVES: The objective was to assess the beneficial and harmful effects of interventions or combination of interventions for paracetamol overdose. SEARCH STRATEGY: The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Library, MEDLINE, EMBASE, and text searches were combined (until July 2001). SELECTION CRITERIA: Randomised clinical trials (RCTs) and observational studies as well as human volunteer randomised trials were included. The studies could be unpublished or published as an article, an abstract, or a letter and no language limitations were applied. DATA COLLECTION AND ANALYSIS: All the analyses were performed according to the intention to treat. The methodological quality of the included trials was evaluated by components of methodological quality. MAIN RESULTS: Nine RCTs (all small and of low methodological quality), one quasi-randomised trials, 37 observational studies, and nine randomised trials including human volunteers were identified. It was impossible to perform meta-analyses including more than two RCTs. Activated charcoal, gastric lavage, and ipecacuanha are able to reduce the absorption of paracetamol but the clinical benefit is unclear. Of these, activated charcoal seems to have the best risk-benefit ratio. N-acetylcysteine seems preferable to placebo/supportive treatment (relative risk of mortality in patients with fulminant hepatic failure = 0.65; 95% confidence interval 0.43 to 0.99), dimercaprol, and cysteamine, but N-acetylcysteine's superiority to methionine is unproven. It is not clear which N-acetylcysteine treatment protocol offers the best efficacy. No evidence supports haemoperfusion or cimetidine for paracetamol overdose. Liver transplantation has the potential to be life saving in fulminant hepatic failure, but further refinement of selection criteria for liver transplantation and evaluation of the long-term outcome are required. REVIEWER'S CONCLUSIONS: This systematic Review has highlighted a paucity of RCTs on interventions for paracetamol overdose. Activated charcoal seems the best choice to reduce paracetamol absorption. N-acetylcysteine should be given to patients with paracetamol overdose. No N-acetylcysteine regime has been shown to be more effective than any other. It is a delicate balance when to proceed to liver transplantation, which may be life saving in patients with a poor prognosis. Interventions for paracetamol overdose need assessment in high-quality, multi-centre RCTs. [References: 114]

Publication Type: Journal Article. Review.

 Link Directly to Fulltext Article at Publisher

<21>

Unique Identifier [PMID]: 11983032

Authors: Dargan PI. Jones AL.

Institution: Specialist Registrar in Medicine and Clinical Toxicology, National Poisons Information Service, Guy's & St Thomas' NHS Trust, London, UK. paul.dargan@gstt.sthames.nhs.uk

Title: Acetaminophen poisoning: an update for the intensivist. [Review] [16 refs]

Source: Critical Care (London). 6(2):108-10, 2002 Apr.

Abstract: Acetaminophen overdose is common and can result from deliberate/nonstaggered or accidental/staggered ingestion. Patients presenting within 24 h of an acetaminophen overdose can safely be managed on medical wards. Early management of nonstaggered overdose is guided by the plasma acetaminophen concentration, whereas management of accidental/staggered ingestion is guided by ingested dose. Ingested dose and time from ingestion to presentation are important prognostic factors in accidental/staggered ingestion. Acetaminophen-induced acute liver failure (ALF) requires meticulous supportive care in an intensive care unit (ICU), with early identification and transfer of patients who are likely to require liver transplantation to a specialist liver centre. The modified King's College Hospital criteria (incorporating lactate into the traditional criteria) represent the best tool for identifying patients who require transplantation. [References: 16]

Publication Type: Journal Article. Review. Review, Tutorial.

 Link Directly to Fulltext Article at Publisher

<24>

Unique Identifier [PMID]: 11444723

Authors: Kozer E. Koren G.

Institution: Division of Clinical Pharmacology and Toxicology, The Hospital for Sick Children, Toronto, Ontario, Canada. eran.kozer@sickkids.on.ca

Title: Management of paracetamol overdose: current controversies. [Review] [88 refs]

Source: Drug Safety. 24(7):503-12, 2001.

Abstract: Paracetamol (acetaminophen) is one of the most frequently used analgesics, and is the most commonly used substance in self-poisoning in the US and UK. Paracetamol toxicity is manifested primarily in the liver. Treatment with N-acetyl-cysteine (NAC), if started within 10 hours from ingestion, can prevent hepatic damage in most cases. Pharmacokinetic data relating plasma paracetamol concentration to time after ingestion have been used to generate a 'probable hepatoxicity line' to predict which cases of paracetamol overdose will result in hepatotoxicity and should be treated with NAC. However, later studies use a 25% lower line as their 'possible hepatotoxicity line'. Although adopting the original line may save considerable resources, further studies are needed to determine whether such an approach is safe. On the basis of the metabolism of paracetamol, several risk factors for paracetamol toxicity have been proposed. These risk factors include long term alcohol (ethanol) ingestion, fasting and treatment with drugs that induce the cytochrome P450 2E1 enzyme system. Although some studies have suggested that these risk factors may be associated with worse prognosis, the data are inconclusive. However, until further evidence is available, we suggest that the lower line should be used when risk factors are present. In Canada and the UK, the intravenous regimen for NAC is used almost exclusively; in the US, an oral regimen is used. Both regimens have been shown to be effective. There is no large scale study with direct comparison between these 2 therapeutic protocols and controversy still exists as to which regimen is superior. During the last few years there has been an increase in the number of reports of liver failure associated with prolonged paracetamol administration for therapeutic reasons. The true incidence of this phenomenon is not known. We suggest testing liver enzyme levels if a child has received more than 75 mg/kg/day of paracetamol for more than 24 hours during febrile illness, and to treat with NAC when transaminase levels are elevated. Paracetamol overdose during pregnancy should be treated with either oral or intravenous NAC according to the regular protocols in order to prevent maternal, and potentially fetal, toxicity. Unless severe maternal toxicity develops, paracetamol overdose does not appear to increase the risk for adverse pregnancy outcome. [References: 88]

Publication Type: Journal Article. Review. Review, Tutorial.

Resident Report / Department of Medicine & Grady Branch Library

Emory University School of Medicine

2005 Edition

Participating Faculty:  Carlos Del Rio MD  / Joyce Doyle MD / Lorenzo Difrancesco MD / Erich Folch MD / Alicia Hidron  MD  

Contact: Karl Woodworth